Proniosomal transdermal therapeutic system of losartan potassium: development and pharmacokinetic evaluation.
ABSTRACT The purpose of the current study was to investigate the feasibility of proniosomes as transdermal drug delivery system for losartan potassium. Different preparations of proniosomes were fabricated using different nonionic surfactants, such as Span 20, Span 40, Span 60, Span 80, Tween 20, Tween 40, and Tween 80. Different formulae were prepared and coded as PNG-1 (proniosomal gel-1) to PNG-7. The best in vitro skin permeation profile was obtained with proniosomal formulation PNG-2 in 24 h. The permeability parameters such as flux, permeability coefficient, and enhancement ratio were significant for PNG-2 compared with other formulations (P < 0.05). This optimized PNG-2 was fabricated in the form of transdermal patch using HPMC gel as a suitable base. Proniosomal transdermal therapeutic system (PNP-H) was found to be the optimized one as it gave better release of drug and better permeation in a steady-state manner over a desired period of time, that is, 24 h through rat skin. In vivo pharmacokinetic study of PNP-H showed a significant increase in bioavailability (1.93 times) compared with oral formulation of losartan potassium. The formulation appeared to be stable when stored at room temperature (30 +/- 2 degrees C) and at refrigeration temperature (4 +/- 2 degrees C) for 45 days.
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ABSTRACT: INTRODUCTION: In recent years, nanoemulsions have been investigated as potential drug delivery vehicles for transdermal and dermal delivery of many compounds especially hydrophobic compounds in order to avoid clinical adverse effects associated with oral delivery of the same compounds. Droplet size and surface properties of nanoemulsions play an important role in the biological behavior of the formulation. AREAS COVERED: In this review, current literature of transdermal and dermal delivery of hydrophobic compounds both in vitro as well as in vivo has been summarized and analyzed. EXPERT OPINION: Nanoemulsions have been formulated using a variety of pharmaceutically acceptable excipients. In many cases of dermal and transdermal nanoemulsions, the skin irritation or skin toxicity issues on human beings have not been considered which needs to be evaluated properly. In the last decade, much attention has been made in exploring new types of nanoemulsion-based drug delivery system for dermal and transdermal delivery of many hydrophobic compounds. This area of research would be very advantageous for formulation scientists in order to develop some nanoemulsion-based formulations for their commercial exploitation and clinical applications.Expert Opinion on Drug Delivery 06/2012; 9(8):953-74. · 4.87 Impact Factor
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ABSTRACT: Non-ionic surfactant vesicles (NSVs) were proposed for the pulmonary delivery of glucocorticoids such as beclomethasone dipropionate (BDP) for the treatment of inflammatory lung diseases, e.g. asthma, chronic obstructive pulmonary disease and various type of pulmonary fibrosis. The thin layer evaporation method followed by sonication was used to prepare small non-ionic surfactant vesicles containing beclomethasone dipropionate. Light scattering experiments showed that beclomethasone dipropionate-loaded non-ionic surfactant vesicles were larger than unloaded ones and showed a significant (P<0.001) decrease of the zeta potential. The morphological analysis, by freeze-fracture transmission electron microscopy, showed the maintenance of a vesicular structure in the presence of the drug. The colloidal and storage stability were evaluated by Turbiscan Lab Expert, which evidenced the good stability of BDP-loaded non-ionic surfactant vesicles, thus showing no significant variations of mean size and no colloidal phase segregation. Primary human lung fibroblast (HLF) cells were used for in vitro investigation of vesicle tolerability, carrier-cell interaction, intracellular drug uptake and drug-loaded vesicle anti-inflammatory activity. The investigated NSVs did not show a significant cytotoxic activity at all incubation times for concentrations ranging from 0.01 to 1 μM. Confocal laser scanning microscopy showed vesicular carrier localization at the level of the cytoplasm compartment, where the glucocorticoid receptor (target site) is localized. BDP-loaded non-ionic surfactant vesicles elicited a significant improvement of the HLF intracellular uptake of the drug with respect to the free drug solution, drug/surfactant mixtures and empty vesicles used as references. The treatment of HLF cells with BDP-loaded non-ionic surfactant vesicles determined a noticeable increase of the drug anti-inflammatory activity by reducing the secretion of both constitutive and interleukin-1β-stimulated nerve growth factor (as inflammatory index) of 68% and 85%, respectively. Obtained data indicate that the investigated NSVs represent a promising tool as a pulmonary drug delivery system.Journal of Controlled Release 10/2010; 147(1):127-35. · 7.63 Impact Factor
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ABSTRACT: Abstract Context: Angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) are some of the most commonly prescribed medications for hypertension. Objective: Most of all conventional dosage forms of ARBs and ACEIs undergo extensive first-pass metabolism, which significantly reduces bioavailability. Majority of ARBs and ACEIs are inherently short acting due to a rapid elimination half-life. In addition, oral dosage forms of ARBs and ACEIs have many high incidences of adverse effects due to variable absorption profiles, higher frequency of administration and poor patient compliance. Methods: Many attempts have been made globally at the laboratory level to investigate the skin permeation and to develop transdermal therapeutic systems of various ARBs, ACEIs and other anti-hypertensives, to circumvent the drawbacks associated with their conventional dosage form. Results: This manuscript presents an outline of the transdermal research specifically in the area of ARBs, ACEIs and other anti-hypertensives reported in various pharmaceutical journals. Conclusion: The transdermal delivery has gained a significant importance for systemic treatment as it is able to avoid first-pass metabolism and major fluctuations of plasma levels typical of repeated oral administration. As we can experience from this review article that transdermal delivery of different ARBs and ACEIs improves bioavailability as well as patient compliance by many folds. In fact, the rationale development of some newer ARBs, ACEIs and other anti-hypertensives transdermal systems will provide new ways of treatment, circumventing current limitations for conventional dosage forms.Drug delivery. 07/2014;